The present proposal is undertaken to study the effect of endotoxic shock on myocardial metabolism in normal and alloxan-diabetic dogs, and to delineate the mechanisms responsible for the metabolic alterations. Finally, attempts will be made to prevent the onset or delay the progression of cellular derangements induced by endotoxin in normal and diabetic dogs. The proposed experiments involove uptake and oxidation of substrates by the myocardium, translocation of adenine nucleotides across mitochondrial membrane, and sodium-potassium membrane pump activity. The information to be obtained from these studies will be useful in the understanding of the pathophysiology of heart during endotoxic shock in normal dogs, as well as dogs which are made diabetic prior to the onset of shock.